Described herein are methods using CRISPR-Cas9 and DNA templates that can generate chimeric antigen receptors (CARs) on T cells to target the cell surface protein urokinase Plasminogen Activator Receptor (uPAR) on senescent cells. Also described are methods of preparing CAR T cells, their use to treat neurodegenerative disease, stroke, craniocerebral trauma and/or accident, or elderly individuals in need of treatment for aging.

A recombinant immune cell expresses a heterologous IgG Fc receptor. In some embodiments, the heterologous IgG Fc receptor can be a chimeric IgG Fc receptor. Generally, the chimeric IgG Fc receptor includes an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain generally includes a sufficient portion of CD64 to bind to an IgG Fc region. The intracellular domain of the chimeric IgG Fc receptor includes a sufficient portion of an Fc receptor allowing immunoreceptor tyrosine-based activation motif (ITAM) to initiate cell signaling when an IgG Fc region binds to the extracellular domain.

The technology described herein is directed to Natural Killer (NK) cell CAR polypeptides comprising intracellular signaling domains, intracellular costimulatory domains, and/or transmembrane domains from NK-associated polypeptides. In various aspects, described herein are polynucleotides, vectors, or cells expressing said NK CAR polypeptides, and pharmaceutical compositions comprising said NK CAR polypeptides, polynucleotides, vectors, or cells. Also described herein are methods of using said NK CAR polypeptides, for example to treat various diseases and disorders, such as cancer or infectious diseases.

Disclosed herein are fibroblast activation protein (FAP)-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and/or CARs for the treatment of, for example, a cancer.

Chimeric antigen receptors targeting CD20 and preparation methods thereof are provided. The antigen binding region of the chimeric antigen receptor may include a heavy chain variable region shown in SEQ ID NOs: 7, 9 or 33 and a light chain variable region shown in SEQ ID NOs: 11, 13 or 35.

The present invention provides chimeric antigen receptors (CAR) and methods of use in the treatment of diseases and disorders.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-MUC16 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.

The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising a modification in an endogenous gene locus encoding SOX and/or ID3. Methods for assessing and treating T cell dysfunction are also provided.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-MUC16 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.

The invention pertains to bispecific antibodies having two antigen binding specificities, one binding to an epitope of NKG2-D type II integral membrane protein (NKG2D) and one binding to an antigen associated with a disease, preferably a tumor associated- or tumor specific antigen, such as ErbB2 (HER2), CD19, CD20, GD2, PD-L1, EGFR, or EGFRvIII. The bispecific molecules of the invention are preferably applied in the context of the treatment of tumor diseases or infectious diseases. Surprisingly it was found that the use of NKG2D binding specificities that bind in a competitive manner to the NKG2D receptor with its natural ligands such as MICA reduces or prevents the inhibitory effect of ligand shedding. Another advantage of the present invention lies in a synergistic combination of the bispecific molecules of the invention and chimeric antigen receptor (CAR) based therapy. Further provided are methods for the production of the antibodies of the invention, nucleic acids encoding the bispecific antibodies or fragments thereof, pharmaceutical composition and recombinant cells comprising nucleic acids or antibody proteins.